Black and White populations in the United States manifest distinctly different profiles of tobacco-related and/or alcohol-related neoplasms. Analyses of smoking patterns by these groups have not revealed a higher intake of cigarettes per day to account for the observed higher prevalence of aerodigestive cancer among Blacks or differences in type of tobacco products which might help explain the observed lower rates of urinary bladder cancer among black populations. The current proposal is a metabolic epidemiological study designed to elucidate whether differences in metabolic capacity resulting in differences in exposure of individuals and target tissues to activated tobacco smoke carcinogens are responsible for the observed variations in site-specific cancer incidence. The proposed five.year investigation will consist of three major studies. In study #1, a total of 320 healthy smokers, 80 of each race-sex combination will be recruited. In this cross-sectional study, questionnaire data on lifestyle, smoking history and diet will be obtained. In addition, several new biomarkers for exposure and susceptibility to tobacco-smoke carcinogens will be studied including acetylation phenotype, P-450IA2 phenotype, hemoglobin adducts from 4-aminobiphenyl and NNK, urinary NNK metabolites and glutathione S-transferase MI genotype. In study #2, the association between NNAL-glucuronidation phenotype and other selected biomarkers with the risk for adenocarcinoma of the lung will be investigated using a case-control design. Finally, in study #3, the association of acetylation and P-450IA2 phenotype and other selected biomarkers with bladder cancer risk will be investigated in Blacks and Whites using a case-control design. A total of 140 cases and controls will be recruited for both studies #2 and #3. Overall, the project attempts to provide mechanisms whereby differences in site-specific cancer incidence between the races might be elucidated and draws upon the expertise of the American Health Foundation large data base in tobacco-related cancers and upon our ability to integrate appropriate questionnaire information and laboratory data obtained from diverse populations. The unique approach in metabolic epidemiology will enable us to more fully understand the observed diversity in cancer prevalence.